The maintenance of adequate and safe access to the circulation is critical to the hemodialysis treatment of patients with ESRD. The three major categories of access are fistulas, grafts, and catheters. Fistulas are the preferred access because of their longer unassisted long-term survival compared to grafts. Unfortunately, thrombosis of the fistulas, within the first few weeks of placement, occurs in 12-30%. Another 10-30% of fistulas do not develop adequately to support the demands of high-efficiency hemodialysis. In either situation, a new access is usually required. If fistulas are not feasible (usually due to small veins), grafts are placed. Although the early function of grafts is good, 53% require intervention within a year of placement to restore adequate function. The likely culprit is myointimal hyperplasia causing stenosis at the venous outflow of the graft. When fistulas or grafts are not functional, tunneled catheters are needed to continue dialysis treatments. Dialysis catheters are associated with bacteremia and increased mortality. The overall goal of the DAC Study is to improve fistula and graft vascular access viability. The specific aim for the Fistula Arm is to determine if the 6-week administration of the anti-platelet drug, clopidogrel, increases the patency rate of newly placed fistulas. A secondary aim is to determine if clopidogrel increases the number of fistulas that are suitable for dialysis. The specific aim for the Graft Arm is to determine if continuous administration of Aggrenox (containing dipyridamole and small amounts of aspirin) prolongs the primary unassisted patency in newly constructed grafts. The presumed mechanism is inhibition of smooth muscle hyperplasia. Monthly measurements of access flow rate are done to detect hemodynamically significant stenoses before the grafts clot. Grafts who meet the criteria are submitted to angiography. A 50% stenosis triggers the repair of the graft (a primary end-point along with clotting of the graft). Enrollment in this large, double-blinded, placebo controlled trial began 1-7-03 and continues. Data is collated and analyzed at the Data Coordinating Center at the Cleveland Clinic. An external advisory committee monitors safety and efficacy. If either or both of the drugs are found to be beneficial, the morbidity, and possibly mortality, of hemodialysis patients will improve substantially. The health care cost of maintaining adequate vascular access should also decrease from its current rate of over one billion dollars per year.